In 1954, Gates reported the first total synthesis of morphine 1 by an ingenious yet simple route, utilizing a .beta.-dihydrothebainone-dihydrothebainone isomerization sequence in order to adjust the C.sub.14 stereocenter. Since Gates's original approach, a total of 16 syntheses have been reported. The majority (nine of them), including the most recent one of Overman, proceed via 1-benzylisoquinoline intermediates, with the crucial step being C.sub.12 -C.sub.13 bond formation. These syntheses are formalized by intercepting Gates's dihydrothebainone (or .beta.dihydrothebainone) or by producing the baine. The most efficient routes to date, those of Rice and Beyerman, have also used this strategy. Despite a number of attempts, only one successful synthesis (Evans) utilized a C.sub.10 -C.sub.11 closure late in the synthesis in order to complete the morphinan skeleton, followed by adjustment of stereochemistry at C.sub.14. ##STR3##
In 1994, Parker reported the full details of a radical cascade approach (published in a preliminary form in 1992)to racemic 1.